Demyelination determinants map to the spike glycoprotein gene of coronavirus mouse hepatitis virus
Demyelination determinants map to the spike glycoprotein gene of coronavirus mouse hepatitis virus
复制标题
DOI：
10.1128/jvi.74.19.9206-9213.2000
复制
发表时间：
2000-10-01
影响因子：
5.4
通讯作者：
Lavi, E
中科院分区：
文献类型：
--
作者：
Das Sarma, J;Fu, L;Lavi, E
脱髓鞘是人类免疫介导的神经系统疾病多发性硬化症的病理标志，其可由病毒感染触发或加重。已经开发了几种实验动物模型来研究病毒诱导的脱髓鞘机制，包括小鼠中的冠状病毒小鼠肝炎病毒（MHV）感染。MHV的囊膜刺突（S）糖蛋白包含病毒-宿主相互作用所必需的性质的决定因素。然而，MHV诱导的脱髓鞘的分子决定因素仍然是未知的。为了研究MHV诱导脱髓鞘的机制，我们检测了MHV的S基因是否包含脱髓鞘的决定因素以及脱髓鞘是否与病毒持续存在有关。使用靶向RNA重组，我们用一种密切相关的非脱髓鞘病毒（MHV-2）的S基因替换了脱髓鞘病毒（MHV-A59）的S基因。在MHV-A59背景下含有来自MHV-2的S基因的重组病毒（Penn 98 -1和Penn 98 -2）表现出持续阳性、脱髓鞘阴性表型。因此，脱髓鞘的决定因素映射到MHV的S基因。此外，病毒持续存在不足以诱导脱髓鞘，尽管它可能是脱髓鞘发展的先决条件。
Demyelination is the pathologic hallmark of the human immune-mediated neurologic disease multiple sclerosis, which may be triggered or exacerbated by viral infections. Several experimental animal models have been developed to study the mechanism of virus-induced demyelination, including coronavirus mouse hepatitis virus (MHV) infection in mice. The envelope spike (S) glycoprotein of MHV contains determinants of properties essential for virus-host interactions. However, the molecular determinants of MHV-induced demyelination are still unknown. To investigate the mechanism of MHV-induced demyelination, we examined whether the S gene of MHV contains determinants of demyelination and whether demyelination is linked to viral persistence. Using targeted RNA recombination, we replaced the S gene of a demyelinating virus (MHV-A59) with the S gene of a closely related, nondemyelinating virus (MHV-2). Recombinant viruses containing an S gene derived from MHV-2 in an MHV-A59 background (Penn98-1 and Penn98-2) exhibited a persistence-positive, demyelination-negative phenotype. Thus, determinants of demyelination map to the S gene of MHV, Furthermore, viral persistence is insufficient to induce demyelination, although it may be a prerequisite for the development of demyelination.